What is the concern when fibrates are used with statins?

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The main concern when fibrates are used with statins is an increased risk of muscle injury, including myopathy and rhabdomyolysis. This happens because fibrates, especially gemfibrozil, can raise statin exposure by inhibiting their metabolism and hepatic uptake, making the muscles more susceptible to toxicity. Fenofibrate poses a lower risk than gemfibrozil but is not risk-free when combined with statins. In practice, if this combination is necessary, use the lowest effective statin dose, prefer fenofibrate over gemfibrozil, and monitor for muscle symptoms and creatine kinase levels.